Alpha-2 adrenergic receptors mediate several important functions of the endogenous catecholamines in both the central and peripheral nervous systems. Several clinically important drugs appear to produce their pharmacologic effects through an interaction at alpha-2 receptors. There now exists considerable evidence indicating significant differences in the pharmacological characteristics and regulation of mammalian alpha-2 adrenergic receptors from various tissues and species. We suggest that differences in the pharmacological properties and in the regulation (mechanism of action) of alpha-2 adrenergic receptors may be due to differences in the structure of the alpha-2 adrenergic receptor complex. To test this hypothesis, it is proposed to compare in various tissues and species: (1) The rank order and relative potencies of various adrenergic drugs using both radioligand binding and functional assays; (2) The thermal stability and pH optima of radioligand binding; (3) The functional size of the receptor complex using target analysis (radiation inactivation); (4) The apparent molecular size determined by gel filtration and sucrose density gradient centrifugation of receptor preparations solubilized in the presence and absence of agonist; and (5) The apparent molecular weight from SDS gel electrophoresis of partially purified receptors labeled with a photoaffinity probe. These studies should help to resolve the present confusion in classification of alpha receptors and may lead to more selective alpha adrenergic drugs for clinical use.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032931-02
Application #
3344490
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1985-06-01
Project End
1988-05-31
Budget Start
1986-06-01
Budget End
1987-05-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Murphy, T J; Bylund, D B (1988) Oxymetazoline inhibits adenylate cyclase by activation of serotonin-1 receptors in the OK cell, an established renal epithelial cell line. Mol Pharmacol 34:1-7
Bylund, D B; Rudeen, P K; Petterborg, L J et al. (1988) Identification of alpha 2-adrenergic receptors in chicken pineal gland using [3H]rauwolscine. J Neurochem 51:81-6
Bylund, D B; Ray-Prenger, C; Murphy, T J (1988) Alpha-2A and alpha-2B adrenergic receptor subtypes: antagonist binding in tissues and cell lines containing only one subtype. J Pharmacol Exp Ther 245:600-7
Murphy, T J; Bylund, D B (1988) Characterization of alpha-2 adrenergic receptors in the OK cell, an opossum kidney cell line. J Pharmacol Exp Ther 244:571-8
Bylund, D B (1988) Subtypes of alpha 2-adrenoceptors: pharmacological and molecular biological evidence converge. Trends Pharmacol Sci 9:356-61
Jones, S B; Toews, M L; Turner, J T et al. (1987) Alpha 2-adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production. Proc Natl Acad Sci U S A 84:1294-8
Petrash, A C; Bylund, D B (1986) Alpha-2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain. Life Sci 38:2129-37
Bylund, D B (1986) Graphic presentation and analysis of inhibition data from ligand-binding experiments. Anal Biochem 159:50-7
Kawahara, R S; Bylund, D B (1985) Solubilization and characterization of putative alpha-2 adrenergic isoceptors from the human platelet and the rat cerebral cortex. J Pharmacol Exp Ther 233:603-10
Turner, J T; Ray-Prenger, C; Bylund, D B (1985) Alpha 2-adrenergic receptors in the human cell line, HT29. Characterization with the full agonist radioligand [3H]UK-14,304 and inhibition of adenylate cyclase. Mol Pharmacol 28:422-30

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